1. Field of the Invention
The present invention relates to a programmable mask used in a photolithography process for fabricating a biomolecule array and a method of fabricating a biomolecule array using the same and, more particularly, to a programmable mask which can increase a contrast ratio of transmittance versus extinction of light incident to a liquid crystal which constitutes each pixel by irradiating parallel ultraviolet (“UV”) light generated from an external parallel light exposure system to a certain pixel and using a vertically aligned liquid crystal panel or an LC panel having no spacer, and a method of fabricating a biomolecule array using the same.
2. Discussion of Related Art
A region comprised of one kind of biomolecule in a biomolecule array formed on a substrate is hereinafter referred to as a cell for convenience and clarity.
Researches on work for performing simultaneously various kinds of experiments using the biomolecule or polymer array have been heavily performed. The biomolecule array includes a polypeptides array, a nucleic acid (DNA, RNA) array, etc. One of the most important things for such a research is to effectively form a low-cost and high-purity array on a substrate.
A typical method of fabricating the biomolecule or polymer array includes a spotting method in which a micro robot moves three-dimensionally to selectively drop a biochemical material onto a desired location, a photolithography method which selectively irradiates light to a desired location to change a surface so that a coupling reaction between the surface and the biomolecule occurs at a certain location, and an electronic addressing method which adjusts electrode voltage of a microelectrode array such that a biomolecule is fixed only to a certain electrode.
The spotting method includes a contact printing method which stains with a solution as a marker is stamped on a paper, and a non-contact printing method which drops a solution. The contact printing method is performed in order of loading, printing and washing by an XYZ robot. Since a pin having a groove formed on its end like a point of a fountain pen is used, it is possible to control sample volume with reproducibility, and loading a sample once makes it possible to print several times. However, there is a disadvantage in that it is a limitation to increasing the number of arrays per unit area. The non-contacting printing method includes a dispensing method and an ink-jet printing method. The dispensing method is a method which drops a solution as in a micropipette, and the ink-jet printing method is a method which gives fine pressure to an ink reservoir to spout a solution out. The ink-jet printing can finely adjust a sample solution to a nano liter level, thereby increasing the number of arrays per unit area. However, since each sample solution needs the ink reservoir and the number of the ink reservoir to be mounted to the robot is limited, the ink-jet printing method can be used only in the case of fabricating an array using a small number of sample solutions.
The electronic addressing method is a method which fixes a biomolecule using a voltage control function of a microelectrode array, and includes a method which moves the biomolecule with an electric charge to an electrode surface to cause physical chemical coupling, and a method which fixes the biomolecule inside a thin film when the thin film is formed by electrochemical deposition (Consnier, “Biomolecule immobilization on electrode surfaces by entrapment or attachment to electrochemically polymerized films. A view” Biosensors & Bioelectronics 14: pp. 443-456 (1999)). For example, since a DNA has a strong negative charge, if an electrode has a positive charge, the DNA moves toward the electrode. At this time, if the physical chemical coupling is formed between the DNA and the electrode, the DNA is fixed to the electrode (U.S. Pat. No. 5,605,662). However, the electronic addressing method has problems in that it is more difficult to apply when the number of arrays is many, and it basically needs a microelectrode array. Besides, a method which electrochemically varies pH around the electrode to selectively fix a location of the biomolecule was developed. Using this concept, Combimatrix Corporation has suggested a method which location-selectively synthesizes an oligonucleotide to a microelectrode (U.S. Pat. No. 6,090,302, smith et al.). However, this method also has problems in that yield of each reaction is low and purity of each cell is low.
As a conventional method of fabricating a biomolecule array, a method using a liquid crystal display (“LCD”) type programmable mask which can control transmittance of light instead of a photo mask and a micromachined mirror array has been suggested (U.S. Pat. No. 6,271,957, KR Patent No. 2001-0002915). However, all of the conventional methods described above just suggest only a concept using an LCD without any description on LCD requirement for patterning biomolecules, i.e., an LCD type to improve a contrast ratio which is most important in transmittance and extinction of light, and incident UV-light requirement, i.e., any statement that parallelism of incident light is important. Furthermore, U.S. Pat. No. 6,271,957 suggests only a simple concept without any statement that a spacer degrades improvement of contrast.
A biomolecule array is formed on a substrate by the photoreactions repeatedly caused by controlling light transmittance of each pixel of the LCD type programmable mask. It is ideal that a light extinction rate of a pixel which light should be shielded is close to zero (0). In this case, contrast will be infinite, and if such an LCD is employed, a programmable mask will be ideal, and an ideal DNA microarray will be fabricated.
However, since ideal contrast does not exist, a programmable mask which satisfies the followings is needed to get the maximum contrast ratio.
First, in order to increase the contrast ratio, parallel UV-light which is vertically irradiated to an LCD panel is needed. Second, in order to increase the contrast ratio, a liquid crystal should be aligned vertically. Third, in order to increase the contrast ratio, an LCD panel having no spacer should be used.
In order to form the biomolecule or polymer array as described above, an LCD type programmable mask which can resolve the above problems should be used.